H-Y: Development of a serological assay for H-Y antigen has greatly facilitated study of the H-Y (Histocompatibility-Y) system. We are pursuing two major lines of investigation: (a) We find the same or a cross-reacting H-Y antigen in all vertebrate classes and species so far tested (in species in which the female is heterogametic (XY) the female rather than the male is H-Y+). Such evolutionary conservation of H-Y structure implies a vital function. Our hypothesis is that H-Y is the determinant of primary sex. Our plans include more extensive study of the phylogenetic representation of H-Y, especially for the light this may throw on the vexed question of primary sex determination. (b) Because we have so far found no exception to the rule that in XY-male species the H-Y+ phenotype is invariably and exlusively associated with at least rudimentary testicular development, H-Y typing offers entirely new opportunities for the study and diagnosis of aberrations of sexual development in man. Our plans include continued investigation of such clinical material. Sk: We now have strong evidence for the existence of at least two genetically unlinked Sk systems in mice. Our plans include experiments designed to settle conclusively the question whether Sk-determined rejection by chimeras is in fact mediated by a donor cell population that has lost self-tolerance through residence in an antigen-free environment, and other experiments to determine whether self-tolerance is maintained in the normal mouse by circulating Sk antigen. BIBLIOGRAPHIC REFERENCES: Ohno, S., Wachtel, S.S., Koo, G.C. and Christian, L. A hormone like role of H-Y antigen in the bovine freemartin gonad. Nature. In press. 1976. Wachtel, S.S., Koo, G.C. and Ohno, S. H-Y antigen and male development. In New Concepts of the Testis in Normal and Infertile Men: Morphology, Physiology and Pathology. P. Troen and H. Nankin, editors. Raven Press. New York. In press. 1976.